Tissue Engineering and Regenerative Medicine

We recently showed that placental-derived mesenchymal stem/stromal cells (PMSC) enhance endothelial cell viability and network formation of endothelial cells in vitro and induce angiogenesis in a mouse model in vivo by the secretion of paracrine factors or direct cell-cell contact. Thus, beside potential therapeutic aspects in disorders caused by insufficient angiogenesis such as chronic wounds, PMSC are promising tools for supporting vessel formation in engineered tissue constructs. Here, we assessed the impact of PMSC on the integrity and stability of endothelial cells in vascular grafts exposed to shear stress. ePTFE grafts were used to culture endothelial cells derived from the human placenta (hPEC) and PMSC in a 3D tissue culture model. hPEC were attached to the inner graft surface and a constant low (0.015 dyne/cm2) or physiological flow (0.92 dyne/cm2) was applied by a perfusion system. hPEC were supported by PMSC attached to the outer graft surface.PMSC improved the viability of hPEC exposed to 0.015 and 0.92 dyne/cm2 as shown by a decreased LDH release of 18% and 47%, respectively. Angiogenesis array analysis revealed that hPEC exposed to 0.92 dyne/cm2 secreted decreased levels of GRO,MCP-1, TIMP1, TIMP2 and angiogenin under co-culture with hAMSC. hPEC exposed to flow stimulated the migration of hAMSC. Our data demonstrate that PMSC improve adhesion, viability, and stability of endothelial cells in perfused vascular prostheses. Increased angiogenic properties and enhanced migration of cells favor endothelialization in order to provide a non-thrombogenic surface of small diameter vascular grafts in clinical use.